TNF and rheumatoid arthritis: For example, the absence of TNF or IL-6 signaling has been found to impair fracture healing (Gerstenfeld et al, 2003a; Yang et al, 2007), whereas persistent and elevated levels of TNF in rheumatoid arthritis are associated with bone destruction (Binder et al, 2013) and systemic daily administration of high-dose TNF in a rat rib fracture model also resulted in impaired healing (Hashimoto et al, 1989).